Recent strides in the field of genetic engineering are generating tremendous excitement. Long in the works at university and company laboratories, the implications of this treatment are far-reaching.

The rapidly emerging immunotherapy approach is called adoptive cell transfer (ACT); it collects and uses patients’ own immune cells to treat their cancer. There are several types of ACT, but the star of the show right now is CAR T-cell therapy, which made medical history this last August when the Food and Drug Administration (FDA) approved the first genetic therapy for widespread use. Called Kymriah, it is being marketed by Novartis, a global healthcare company based in Switzerland.

While genetic therapies promise to treat many types of cancer some day, Kymriah was approved for the treatment of particularly challenging type of leukemia: B-cell acute lymphoblastic leukemia. The FDA called the disease “devastating and deadly,” and said the new treatment fills an “unmet need.”

“Novartis and other companies have been racing to develop gene therapies for other types of cancers, and experts expect more approvals in the near future,” noted New York Times science writer Denise Grady. “FDA Commissioner Scott Grady said that more than 550 types of experimental gene therapy are currently being studied.” Potential T-cell treatments for solid tumors like breast cancer are still on the horizon.

While FDA approval is typically associated with specific medications, Kymriah and related gene therapies are not like drugs that can be dispensed by any physician. The process involves a proscribed sequence of procedures played out over days and weeks.

To customize Kymriah for individual patients, white blood cells called T cells are removed from a patient’s bloodstream at an approved medical center and then frozen, shipped to Novartis in Morris Plains, N.J., for genetic engineering and multiplying, frozen again, and shipped back to the medical center to be dripped into the patient. That processing is expected to take 22 days.

Novartis said the treatment would be available at an initial network of 20 approved medical centers to be certified within a month, a number that would be expanded to 32 by the end of the year.

“HAPPY AND PROUD”

In the Princeton area, Dr. Neel J. Gandhi, a physician at Capital Health System whose practice includes hematology, internal medicine, and medical oncology, said that he is “happy and proud” of recent advances in gene therapy techniques.

Capital Health describes itself as “the region’s leader in providing progressive, quality patient care with significant investments in our exceptional physicians, nurses, and staff, as well as advanced technology.” It is comprised of two hospitals: the Regional Medical Center in Trenton and the Capital Health Medical Center in Hopewell. A facility in Hamilton provides outpatient services.

“My sense is that the oncology community is very happy that the next leap is being taken—this is the first time this type of treatment has been approved and there will be more on the horizon,” said Gandhi.

While acknowledging that treatment advances are “really exciting” and “big, big news for all cancer patients,” there are still, Gandhi notes “a lot of administrative hurdles and road blocks” before gene therapy becomes widely used. Capital Health aspires to eventually be a major cancer treatment center, but it’s not there yet, says Gandhi. “We really need to curb our enthusiasm,” he said. “My gut feeling is that implementation of the new technique is limited to major medical centers.”

“We’ll be watching the news,” said Gandhi with cautious optimism.

In addition to meeting the challenges of site approval, time lags in processing, and so on, the new treatments are extraordinarily expensive. Kymriah will be given to patients just once, and is estimated to cost a whopping $475,000. Novartis has said that if a patient does not respond within the first month after treatment, there will be no charge, and they will provide financial help to families who are uninsured or underinsured. Still, the numbers are daunting, and long-term support will doubtless include many conversations between pharmaceutical companies, hospitals, physicians, insurers, legislators, and, hopefully not least of all, patients.

T CELLS ATTACKING A CANCER CELL (CAR T-CELL THERAPY)

SIDE EFFECTS

While the outcomes of “living drugs” promise to be extraordinary, so are the current costs and potential side effects, which are usually described as acute and even life-threatening.

The revved-up “T cells,” as they are called, are capable of touching off a “cykotine storm” that can cause high fever, lung congestion, low blood pressure, neurological problems, and other complications. In addition to the FDA requirement that participating hospitals and doctors be specially trained and certified to administer the treatment, hospitals also need to stock certain drugs that quell severe reactions.

“It’s very personalized, very labor intensive,” agrees Dr. Eileen Scigliano, associate professor of medicine, hematology, and medical oncology at Mount Sinai Hospital in Manhattan, where clinical trials for similar treatments are taking place. Once a patient is approved for treatment, she said, onsite medical staff—in addition to attending hematologists and oncologists—are put on call to be ready for any emergencies that may occur. An acute bout of colitis, for example, will need the immediate attention of a gastroenterologist.

“LIKE BEING AT A ROCK CONCERT”

The fact that many of the patients who will receive this treatment would otherwise die puts dangerous side effects and prohibitive costs in perspective. “It’s kind of a juggling act,” admits Scigliano. “We need to prevent bad complications without shutting down treatment.”

Scigliano is unabashedly enthusiastic about the strides being made. Researchers had been looking at the immune system for ways to treat cancer for many years. The new Novartis treatment was originally developed by researchers at the University of Pennsylvania. The first child to receive the therapy was Emily Whitehead, who was 6 and near death from leukemia in 2012 when she was treated at Children’s Hospital of Philadelphia. Now 12, she has been free of leukemia for more than five years.

Dr. Carl June, a leader in developing the treatment at the University of Pennsylvania, recently reported his team’s early experiences with it. In 2010 when tests showed that the first patient was leukemia-free a month after being treated, he and his colleagues could not believe it, and they ordered another biopsy for confirmation. “Now, I have to keep pinching myself to see that this happened,” he said.

Attending early conferences where the University of Pennsylvania results were reported was, “like being at a rock concert or hearing The Beatles for the first time. You could hear a pin drop,” said Scigliano, with a kind of wonder. “The arguments were so compelling, and you thought, ‘oh, my God—why didn’t I think of this.’”

DR. CHIARA BONINI, PROFESSOR AT THE SCHOOL OF MEDICINE, UNIVERSITÀ VITA-SALUTE, SAN RAFFAELE, AND VICE DIRECTOR FOR THE DIVISION OF IMMUNOLOGY, TRANSPLANTATION, AND INFECTIOUS DISEASES AT THE OSPEDALE SAN RAFFAELE SCIENTIFIC INSTITUTE, MILAN, ITALY.

A WORLDWIDE EFFORT

There are, in fact, few conversations about singular recognition among researchers in genetic therapies. A remarkably animating factor of ACT research appears to be its highly collaborative nature. One of the most lucid (and moving) accounts of the history of genetically engineered lymphocytes is Dr. Chiara Bonini’s TEDx talk, “How Living Cells Could Help Us Fight Cancer.” Bonini is a professor at the School of Medicine, Università Vita-Salute, San Raffaele, and vice director for the division of immunology, transplantation, and infectious diseases at the Ospedale San Raffaele Scientific Institute, Milan, Italy. The input of scientists from around the world has been key to success, she says. “Even if the journey has just started,” say TEDx organizers, “Chiara’s enthusiasm toward research will lead you towards a world of hope where everything is possible if you can share your challenges with the right team.”

“It was so improbable that this would ever be a commercially-approved therapy, and now it’s the first gene therapy approved in the United States,” said Dr. June in a recent interview. “It’s so different from all the pharmaceutical models.